Monocyclic β-lactam and unexpected oxazinone formation: synthesis, crystal structure, docking studies and antibacterial evaluation

Abstract

Novel monocyclic b-lactam derivatives bearing aryl, phenyl and heterocyclic rings were synthesized as possible antibacterial agents. Cyclization of imines (3h, 3t) with phenylacetic acid in the presence of phosphoryl chloride and triethyl amine did not afford the expected b-lactams. Instead, highly substituted 1,3-oxazin-4-ones (4h, 4t) were isolated as the only product and confirmed by single crystal X-ray analysis of 4t. The results of antibacterial activity showed that compound 4l exhibited considerable antibacterial activity with MIC and MBC values of 62.5 mg/mL against Klebsiella pneumoniae. Cytotoxicity assay on Chinese Hamster Ovary (CHO) cell line revealed non-cytotoxic behavior of compounds 4d, 4h, 4k and 4l up to 200 mg/mL conc. Molecular docking was performed for compound 4l with penicillin binding protein-5 to identify the nature of interactions. The results of both in silico and in vitro evaluation provide the basis for compound 4l to be carried as a potential lead molecule in the drug discovery pipeline against bacterial infections.

Insights into the Photobehavior of Fluorescent Oxazinone, Quinazoline, and Difluoroboron Derivatives: Molecular Design Based on the Structure–Property Relationships

“…Organic luminescent materials are nowadays in the limelight due to their various advantages over the traditional inorganic counterparts, including cheaper production, easier fabrication, and tunable emission wavelength. − Among the diverse candidates of organic fluorescent dyes in the biological and medical fields, the oxazinone and quinazoline derivatives are more prominent because of their intriguing bioactivities: The oxazinone derivatives are reported to be the promising antimicrobial agents and HIV-1 reverse transcriptase inhibitors; − however, as the fluorophores, their relatively lower fluorescence quantum yields restrict the practical uses of fluorescence labeling to report the biochemical reaction sites by themselves. , Likewise, the quinazoline series have been extensively investigated on account of their various bioactivities such as the antibacterial, anticancer, and enzyme-inhibiting properties. − Apart from the appealing bioactivities, their excellent fluorescence properties are also under the spotlight by virtue of the higher fluorescence quantum yields, good photostability, and larger Stokes shifts. − The difluoroboron family, promising to enhance the molecular absorption/emission intensity or even alter the corresponding wavelength, is often employed to improve the optical properties of parent dyes, ,− and thus various difluoroboron derivatives have been designed and reported, which promote the development and broaden the application of organic fluorescent dyes. − …”

N‐Substituted 1,2,3‐Triazolyl‐Appended Indole‐Chalcone Hybrids as Potential DNA Intercalators Endowed with Antioxidant and Anticancer Properties

“…In extension of our work on the synthesis of bioactive small molecule inhibitors, we adopted a simple and efficient synthetic pathway to achieve the title compounds as shown in Scheme . The key intermediate, indole‐chalcone 1 was prepared by condensation of commercially available indole‐3‐aldehyde and 3‐nitroacetophenone in the presence of piperidine.…”

Chrysin Sensitizes Human Lung Cancer Cells to Tumour Necrosis Factor Related Apoptosis-Inducing Ligand (TRAIL) Mediated Apoptosis

“…To understand the mechanism of chrysin towards apoptotic/anti-apoptotic gene, molecular docking was carried out for the chrysin using Auto Dock 4.2 [17]. Lamarckian Genetic Algorithm was used to carry out the docking analysis.…”